Effect of valsartan on the incidence of diabetes and cardiovascular events

John J McMurray; Rury R Holman; Steven M Haffner; M Angelyn Bethel; Björn Holzhauer; Tsushung A Hua; Yuri Belenkov; Mitradev Boolell; John B Buse; Brendan M Buckley; Antonio R Chacra; Fu-Tien Chiang; Bernard Charbonnel; Chun-Chung Chow; Melanie J Davies; Prakash Deedwania; Peter Diem; Daniel Einhorn; Vivian Fonseca; Gregory R Fulcher; Zbigniew Gaciong; Sonia Gaztambide; Thomas Giles; Edward Horton; Hasan Ilkova; Trond Jenssen; Steven E Kahn; Henry Krum; Markku Laakso; Lawrence A Leiter; Naomi S Levitt; Viacheslav Mareev; Felipe Martinez; Chantal Masson; Theodore Mazzone; Eduardo Meaney; Richard Nesto; Changyu Pan; Rudolf Prager; Sotirios A Raptis; Guy E H M Rutten; Herbert Sandstroem; Frank Schaper; Andre Scheen; Ole Schmitz; Isaac Sinay; Vladimir Soska; Steen Stender; Gyula Tamás; Gianni Tognoni; NAVIGATOR Study Group

doi:10.1056/NEJMoa1001121

Effect of valsartan on the incidence of diabetes and cardiovascular events

John J McMurray, Rury R Holman, Steven M Haffner, M Angelyn Bethel, Björn Holzhauer, Tsushung A Hua, Yuri Belenkov, Mitradev Boolell, John B Buse, Brendan M Buckley, Antonio R Chacra, Fu-Tien Chiang, Bernard Charbonnel, Chun-Chung Chow, Melanie J Davies, Prakash Deedwania, Peter Diem, Daniel Einhorn, Vivian Fonseca, Gregory R FulcherZbigniew Gaciong, Sonia Gaztambide, Thomas Giles, Edward Horton, Hasan Ilkova, Trond Jenssen, Steven E Kahn, Henry Krum, Markku Laakso, Lawrence A Leiter, Naomi S Levitt, Viacheslav Mareev, Felipe Martinez, Chantal Masson, Theodore Mazzone, Eduardo Meaney, Richard Nesto, Changyu Pan, Rudolf Prager, Sotirios A Raptis, Guy E H M Rutten, Herbert Sandstroem, Frank Schaper, Andre Scheen, Ole Schmitz, Isaac Sinay, Vladimir Soska, Steen Stender, Gyula Tamás, Gianni Tognoni, NAVIGATOR Study Group

479 Citations (Scopus)

Abstract

Background: It is not known whether drugs that block the renin-angiotensin system reduce the risk of diabetes and cardiovascular events in patients with impaired glucose tolerance. Methods: In this double-blind, randomized clinical trial with a 2-by-2 factorial design, we assigned 9306 patients with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors to receive valsartan (up to 160 mg daily) or placebo (and nateglinide or placebo) in addition to lifestyle modification. We then followed the patients for a median of 5.0 years for the development of diabetes (6.5 years for vital status). We studied the effects of valsartan on the occurrence of three coprimary outcomes: the development of diabetes; an extended composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, arterial revascularization, or hospitalization for unstable angina; and a core composite outcome that excluded unstable angina and revascularization. Results: The cumulative incidence of diabetes was 33.1% in the valsartan group, as compared with 36.8% in the placebo group (hazard ratio in the valsartan group, 0.86; 95% confidence interval [CI], 0.80 to 0.92; P<0.001). Valsartan, as compared with placebo, did not significantly reduce the incidence of either the extended cardiovascular outcome (14.5% vs. 14.8%; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P = 0.43) or the core cardiovascular outcome (8.1% vs. 8.1%; hazard ratio, 0.99; 95% CI, 0.86 to 1.14; P = 0.85). Conclusions: Among patients with impaired glucose tolerance and cardiovascular disease or risk factors, the use of valsartan for 5 years, along with lifestyle modification, led to a relative reduction of 14% in the incidence of diabetes but did not reduce the rate of cardiovascular events. (ClinicalTrials.gov number, NCT00097786.).

Original language	English
Journal	Briefings from the New England Journal of Medicine
Volume	362
Issue number	16
Pages (from-to)	1477-90
Number of pages	14
ISSN	1531-7242
DOIs	https://doi.org/10.1056/NEJMoa1001121
Publication status	Published - 22 Apr 2010

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10.1056/NEJMoa1001121

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McMurray, J. J., Holman, R. R., Haffner, S. M., Bethel, M. A., Holzhauer, B., Hua, T. A., Belenkov, Y., Boolell, M., Buse, J. B., Buckley, B. M., Chacra, A. R., Chiang, F.-T., Charbonnel, B., Chow, C.-C., Davies, M. J., Deedwania, P., Diem, P., Einhorn, D., Fonseca, V., ... NAVIGATOR Study Group (2010). Effect of valsartan on the incidence of diabetes and cardiovascular events. Briefings from the New England Journal of Medicine, 362(16), 1477-90. https://doi.org/10.1056/NEJMoa1001121

McMurray, JJ, Holman, RR, Haffner, SM, Bethel, MA, Holzhauer, B, Hua, TA, Belenkov, Y, Boolell, M, Buse, JB, Buckley, BM, Chacra, AR, Chiang, F-T, Charbonnel, B, Chow, C-C, Davies, MJ, Deedwania, P, Diem, P, Einhorn, D, Fonseca, V, Fulcher, GR, Gaciong, Z, Gaztambide, S, Giles, T, Horton, E, Ilkova, H, Jenssen, T, Kahn, SE, Krum, H, Laakso, M, Leiter, LA, Levitt, NS, Mareev, V, Martinez, F, Masson, C, Mazzone, T, Meaney, E, Nesto, R, Pan, C, Prager, R, Raptis, SA, Rutten, GEHM, Sandstroem, H, Schaper, F, Scheen, A, Schmitz, O, Sinay, I, Soska, V, Stender, S, Tamás, G, Tognoni, G & NAVIGATOR Study Group 2010, 'Effect of valsartan on the incidence of diabetes and cardiovascular events', Briefings from the New England Journal of Medicine, vol. 362, no. 16, pp. 1477-90. https://doi.org/10.1056/NEJMoa1001121

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title = "Effect of valsartan on the incidence of diabetes and cardiovascular events",

abstract = "Background: It is not known whether drugs that block the renin-angiotensin system reduce the risk of diabetes and cardiovascular events in patients with impaired glucose tolerance. Methods: In this double-blind, randomized clinical trial with a 2-by-2 factorial design, we assigned 9306 patients with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors to receive valsartan (up to 160 mg daily) or placebo (and nateglinide or placebo) in addition to lifestyle modification. We then followed the patients for a median of 5.0 years for the development of diabetes (6.5 years for vital status). We studied the effects of valsartan on the occurrence of three coprimary outcomes: the development of diabetes; an extended composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, arterial revascularization, or hospitalization for unstable angina; and a core composite outcome that excluded unstable angina and revascularization. Results: The cumulative incidence of diabetes was 33.1% in the valsartan group, as compared with 36.8% in the placebo group (hazard ratio in the valsartan group, 0.86; 95% confidence interval [CI], 0.80 to 0.92; P<0.001). Valsartan, as compared with placebo, did not significantly reduce the incidence of either the extended cardiovascular outcome (14.5% vs. 14.8%; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P = 0.43) or the core cardiovascular outcome (8.1% vs. 8.1%; hazard ratio, 0.99; 95% CI, 0.86 to 1.14; P = 0.85). Conclusions: Among patients with impaired glucose tolerance and cardiovascular disease or risk factors, the use of valsartan for 5 years, along with lifestyle modification, led to a relative reduction of 14% in the incidence of diabetes but did not reduce the rate of cardiovascular events. (ClinicalTrials.gov number, NCT00097786.).",

author = "McMurray, {John J} and Holman, {Rury R} and Haffner, {Steven M} and Bethel, {M Angelyn} and Bj{\"o}rn Holzhauer and Hua, {Tsushung A} and Yuri Belenkov and Mitradev Boolell and Buse, {John B} and Buckley, {Brendan M} and Chacra, {Antonio R} and Fu-Tien Chiang and Bernard Charbonnel and Chun-Chung Chow and Davies, {Melanie J} and Prakash Deedwania and Peter Diem and Daniel Einhorn and Vivian Fonseca and Fulcher, {Gregory R} and Zbigniew Gaciong and Sonia Gaztambide and Thomas Giles and Edward Horton and Hasan Ilkova and Trond Jenssen and Kahn, {Steven E} and Henry Krum and Markku Laakso and Leiter, {Lawrence A} and Levitt, {Naomi S} and Viacheslav Mareev and Felipe Martinez and Chantal Masson and Theodore Mazzone and Eduardo Meaney and Richard Nesto and Changyu Pan and Rudolf Prager and Raptis, {Sotirios A} and Rutten, {Guy E H M} and Herbert Sandstroem and Frank Schaper and Andre Scheen and Ole Schmitz and Isaac Sinay and Vladimir Soska and Steen Stender and Gyula Tam{\'a}s and Gianni Tognoni and Steen Stender",

note = "2010 Massachusetts Medical Society",

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doi = "10.1056/NEJMoa1001121",

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T1 - Effect of valsartan on the incidence of diabetes and cardiovascular events

AU - McMurray, John J

AU - Holman, Rury R

AU - Haffner, Steven M

AU - Bethel, M Angelyn

AU - Holzhauer, Björn

AU - Hua, Tsushung A

AU - Belenkov, Yuri

AU - Boolell, Mitradev

AU - Buse, John B

AU - Buckley, Brendan M

AU - Chacra, Antonio R

AU - Chiang, Fu-Tien

AU - Charbonnel, Bernard

AU - Chow, Chun-Chung

AU - Davies, Melanie J

AU - Deedwania, Prakash

AU - Diem, Peter

AU - Einhorn, Daniel

AU - Fonseca, Vivian

AU - Fulcher, Gregory R

AU - Gaciong, Zbigniew

AU - Gaztambide, Sonia

AU - Giles, Thomas

AU - Horton, Edward

AU - Ilkova, Hasan

AU - Jenssen, Trond

AU - Kahn, Steven E

AU - Krum, Henry

AU - Laakso, Markku

AU - Leiter, Lawrence A

AU - Levitt, Naomi S

AU - Mareev, Viacheslav

AU - Martinez, Felipe

AU - Masson, Chantal

AU - Mazzone, Theodore

AU - Meaney, Eduardo

AU - Nesto, Richard

AU - Pan, Changyu

AU - Prager, Rudolf

AU - Raptis, Sotirios A

AU - Rutten, Guy E H M

AU - Sandstroem, Herbert

AU - Schaper, Frank

AU - Scheen, Andre

AU - Schmitz, Ole

AU - Sinay, Isaac

AU - Soska, Vladimir

AU - Stender, Steen

AU - Tamás, Gyula

AU - Tognoni, Gianni

AU - NAVIGATOR Study Group

N1 - 2010 Massachusetts Medical Society

PY - 2010/4/22

Y1 - 2010/4/22

N2 - Background: It is not known whether drugs that block the renin-angiotensin system reduce the risk of diabetes and cardiovascular events in patients with impaired glucose tolerance. Methods: In this double-blind, randomized clinical trial with a 2-by-2 factorial design, we assigned 9306 patients with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors to receive valsartan (up to 160 mg daily) or placebo (and nateglinide or placebo) in addition to lifestyle modification. We then followed the patients for a median of 5.0 years for the development of diabetes (6.5 years for vital status). We studied the effects of valsartan on the occurrence of three coprimary outcomes: the development of diabetes; an extended composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, arterial revascularization, or hospitalization for unstable angina; and a core composite outcome that excluded unstable angina and revascularization. Results: The cumulative incidence of diabetes was 33.1% in the valsartan group, as compared with 36.8% in the placebo group (hazard ratio in the valsartan group, 0.86; 95% confidence interval [CI], 0.80 to 0.92; P<0.001). Valsartan, as compared with placebo, did not significantly reduce the incidence of either the extended cardiovascular outcome (14.5% vs. 14.8%; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P = 0.43) or the core cardiovascular outcome (8.1% vs. 8.1%; hazard ratio, 0.99; 95% CI, 0.86 to 1.14; P = 0.85). Conclusions: Among patients with impaired glucose tolerance and cardiovascular disease or risk factors, the use of valsartan for 5 years, along with lifestyle modification, led to a relative reduction of 14% in the incidence of diabetes but did not reduce the rate of cardiovascular events. (ClinicalTrials.gov number, NCT00097786.).

AB - Background: It is not known whether drugs that block the renin-angiotensin system reduce the risk of diabetes and cardiovascular events in patients with impaired glucose tolerance. Methods: In this double-blind, randomized clinical trial with a 2-by-2 factorial design, we assigned 9306 patients with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors to receive valsartan (up to 160 mg daily) or placebo (and nateglinide or placebo) in addition to lifestyle modification. We then followed the patients for a median of 5.0 years for the development of diabetes (6.5 years for vital status). We studied the effects of valsartan on the occurrence of three coprimary outcomes: the development of diabetes; an extended composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, arterial revascularization, or hospitalization for unstable angina; and a core composite outcome that excluded unstable angina and revascularization. Results: The cumulative incidence of diabetes was 33.1% in the valsartan group, as compared with 36.8% in the placebo group (hazard ratio in the valsartan group, 0.86; 95% confidence interval [CI], 0.80 to 0.92; P<0.001). Valsartan, as compared with placebo, did not significantly reduce the incidence of either the extended cardiovascular outcome (14.5% vs. 14.8%; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P = 0.43) or the core cardiovascular outcome (8.1% vs. 8.1%; hazard ratio, 0.99; 95% CI, 0.86 to 1.14; P = 0.85). Conclusions: Among patients with impaired glucose tolerance and cardiovascular disease or risk factors, the use of valsartan for 5 years, along with lifestyle modification, led to a relative reduction of 14% in the incidence of diabetes but did not reduce the rate of cardiovascular events. (ClinicalTrials.gov number, NCT00097786.).

U2 - 10.1056/NEJMoa1001121

DO - 10.1056/NEJMoa1001121

M3 - Journal article

SN - 1531-7242

VL - 362

SP - 1477

EP - 1490

JO - Briefings from the New England Journal of Medicine

JF - Briefings from the New England Journal of Medicine

IS - 16

ER -

Effect of valsartan on the incidence of diabetes and cardiovascular events

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